The PBP2a is a cell wall synthesizing protein, which causes resistivity in methicillin resistant Staphylococcus aureus (MRSA) from β-lactam antibiotics but it is susceptible to 5th generation cephalosporin, ceftobiprole. Ceftobiprole inhibits the growth of MRSA by targeting the PBP2a-mediated cell wall synthesis, but it is reported to have adverse side effects. Due to this, there is a constant need to develop natural alternatives, which are generally free from adverse side effects. Hence in this study, in silico based docking analysis was performed with 37 quercetin derivatives towards PBP2a inhibition and their efficiencies were compared with β-lactam antibiotic, ceftobiprole. The docking studies suggested that quercetin 3-O-rutinoside (ZINC5280805) interacted efficiently with PBP2a, attaining the highest LibDock score (187.32) compared to other quercetin derivatives. The structural stability and dynamics of the identified lead with PBP2a were validated through molecular dynamics simulation. Simulation results such as RMSD, RMSF, and Rg values indicated that the stability of quercetin 3-O-rutinoside with PBP2a was better, with respect to the un-ligated PBP2a. Furthermore, the quercetin 3-O-rutinoside was subjected to an antibacterial susceptibility test and found to have antibacterial activity at 500, 700, and 900 μM concentration. Also, morphological changes in the bacterial colony and bacterial surface were observed using a scanning electron microscope, when MRSA was treated with 900 μM concentration of quercetin 3-O-rutinoside. Collectively, results from this study suggest that the quercetin 3-O-rutinoside has the capability to inhibit PBP2a and hence could be used as an alternative or in combination with other drugs in treating MRSA infection.
Use of phyto-medicine and digitalization of phyto-compounds has been fallen enthralling field of science in recent years. Quercetin, a flavonoid with brilliant citron yellow pigment, is typically found in fruits and leafy vegetables in reasonable amount. Quercetin's potentials as an antioxidant, immune-modulator, antiinflammatory, anti-cancer, and others have been the subject of interest in this review. Although, profiling the insights in to the molecular characterization of quercetin with various targets provided the loop-holes in understanding the knowledge for the aforementioned mechanisms, still necessitates research globally to unearth it completely. Thus, the available science on the synthesis and significant role played by the old molecule - quercetin which does wonders even now have been vividly explained in the present review to benefit the scientific community.
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